This career development award proposal is a five-year plan that will enable the candidate to develop into an independent investigator in the genetics of affective disorders with an emphasis on hormonally-triggered symptoms in women. The candidate is an academic psychiatrist with training in mood disorders who now seeks further training in genetics and genetic epidemiology. Dr. J. Raymond DePaulo, Jr, director of the Affective Disorders Genetics Research Group and Chair of the Johns Hopkins Department of Psychiatry will mentor the candidate on conducting genetic research in the psychiatric patient. Dr. Terri Beaty, Professor at the Johns Hopkins School of Public Health, will mentor the candidate on using statistical methods and genetic epidemiology. Dr. David Rubinow, Professor and Chair of Psychiatry at the University of North Carolina and Dr. Peter Schmidt, Chief of the Unit on Reproductive Endocrinology Studies, will mentor the candidate in both the neurobehavioral effects of gonaldal steroids as well as clinical and phenotypic issues in women's mental health. The training program will be enhanced by a research plan based on the hypothesis that women with postpartum depressive episodes have a genetic vulnerability to times of normal hormonal change that consists of variation in a gene (or genes) that is estrogen responsive. The research plan will take advantage of previously collected family samples of bipolar disorder and recurrent major depression. Based on preliminary data demonstrating the familiality of postpartum depressive episodes in families with major depression and bipolar disorder, the candidate will complete the following three specific aims: 1) complete a linkage analysis for this trait;2) perform association studies, specifically examining genes in regions of interest which contain estrogen-response elements and thus may be susceptible to the hormone fluctuations that occur during the postpartum period;and 3) begin collection of a pilot sample of women with major depression with and without postpartum depression. The proposed research is significant because it will lead to a better understanding of the pathophysiology of postpartum depression in women with mood disorders as well as potentially contribute to understanding the increased rate of depressive episodes observed in women as a group.